Indirect treatment comparison of cabazitaxel for patients with metastatic castrate-resistant prostate cancer who have been previously treated with a docetaxel-containing regimen.

BACKGROUND: The objective of this study was to conduct an indirect treatment comparison between cabazitaxel, abiraterone and enzalutamide to determine the clinical efficacy and safety of cabazitaxel relative to comparators in the treatment of patients with metastatic castrate-resistant prostate cancer who progress on docetaxel-based therapies. METHODS: A systematic literature review was conducted to inform the network meta-analysis of cabazitaxel, abiraterone and enzalutamide. Due to a lack of head-to-head trials, studies with a comparator arm of best supportive care were included in the analysis. Overall survival, progression-free survival, and adverse events were compared within both Bayesian and Frequentist frameworks. The ratios for survival outcomes were estimated using hazard ratios (HR), and the ratios for adverse events between groups were estimated using odds ratios (ORs); uncertainty was reported as 95% confidence (Frequentist) and credible (Baysesian) Intervals. RESULTS: Three of thirteen trials identified for abstraction were relevant for analyses. Median overall survival was not statistically significantly different for abiraterone (HR = 1.04; 95% CI = 0.83-1.28) or enzalutamide (HR = 0.88; 95% CI = 0.69-1.11) when compared to cabazitaxel in the Bayesian analysis. Anaemia (OR = 3.71; 95% CI = 1.01-10.44), diarrhoea (OR = 16.60; 95% CI = 1.41-75.31) and haematuria (OR = 3.88; 95% CI = 1.03-10.09) were more likely to occur in the cabazitaxel group than the abiraterone group, while pyrexia risk was higher in cabazitaxel compared to enzalutamide (OR = 36.23; 95% CI = 1.14-206.40). Frequentist analyses produced similar results. CONCLUSIONS: The scarcity of clinical studies and lack of a common comparator limited analyses. The adverse event results must be interpreted with caution as many were based on small numbers. The results from this analysis indicate comparable survival outcomes and adverse event profiles. As these pivotal studies may not reflect the contemporary treatment landscape and patient profiles, additional research, including head-to-head clinical trials and real world observational studies, should be conducted to further elucidate the beneficial effects of these therapies.

Efficacy and safety of post-docetaxel therapies in metastatic castration-resistant prostate cancer: a systematic review of the literature.

OBJECTIVE: Prostate cancer is a highly prevalent form of cancer in older men and is one of the leading causes of death from cancer in men across the globe. Many therapeutic agents have been approved for patients with metastatic castration-resistant prostate cancer (mCRPC), particularly as a post-docetaxel treatment strategy. The objective of this systematic literature review was to assess published efficacy and safety data for select mCRPC therapies - such as abiraterone, cabazitaxel, and enzalutamide - in the post-docetaxel setting. METHODS: Database searches of MEDLINE, Embase, and Cochrane CENTRAL, in conjunction with hand searches of multiple congress abstracts, yielded 13 randomized studies and 107 non-randomized studies that met the inclusion criteria. RESULTS: Randomized studies demonstrated significant improvements in median overall survival (OS) outcomes over placebo for abiraterone (15.8 vs. 11.2 months) and enzalutamide (18.4 vs. 13.6 months), and similar significant improvements were noted for cabazitaxel over mitoxantrone (15.1 vs. 12.7 months). Differences in progression-free survival (PFS) were similarly significant, although variance in the criteria for measuring PFS may limit the extent to which these outcomes can be compared between studies. Non-randomized evidence included multiple publications from several early access and compassionate use programs with a primary objective to report safety outcomes. Results from these studies largely reflected the findings in randomized trials. CONCLUSIONS: Overall, there is a growing body of evidence for post-docetaxel treatment options available in patients with mCRPC. Further head-to-head trials or indirect treatment comparisons may be a valuable method to assess the comparative efficacy of these therapies.